Thermoregulation is known to interfere with sleep, possibly due to a functional interaction at the level of the preoptic area (POA). Exposure to low ambient temperature (T(a)) induces sleep deprivation, which is followed by sleep rebound after a return to laboratory T(a). As two POA subregions, the ventrolateral preoptic nucleus (VLPO) and the median preoptic nucleus (MnPO), have been proposed to have a role in sleep-related processes, the expression of c-Fos and the phosphorylated form of the cAMP/Ca(2+)-responsive element-binding protein (P-CREB) was investigated in these nuclei during prolonged exposure to a T(a) of -10 degrees C and in the early phase of the recovery period. Moreover, the dynamics of the sleep rebound during recovery were studied in a separate group of animals. The results show that c-Fos expression increased in both the VLPO and the MnPO during cold exposure, but not in a specific subregion within the VLPO cluster counting grid (VLPO T-cluster). During the recovery, concomitantly with a large rapid eye movement sleep (REMS) rebound and an increase in delta power during non-rapid eye movement sleep (NREMS), c-Fos expression was high in both the VLPO and the MnPO and, specifically, in the VLPO T-cluster. In both nuclei, P-CREB expression showed spontaneous variations in basal conditions. During cold exposure, an increase in expression was observed in the MnPO, but not in the VLPO, and a decrease was observed in both nuclei during recovery. Dissociation in the changes observed between c-Fos expression and P-CREB levels, which were apparently subject to state-related non-regulatory modulation, suggests that the sleep-related changes observed in c-Fos expression do not depend on a P-CREB-mediated pathway.